The purpose of this program is to describe the sequence of events involved in the hormone stimulation of the liver which will result in the synthesis of a specific plasma protein. The model system to be used is the hepatic synthesis of the male sex-dependent urinary protein (alpha 2u-globulin). Our present knowledge concerning this protein indicates that both testosterone and a glucocorticoid are required to stimulate its hepatic synthesis. Consideration will be given to effects of these hormones on amino acid uptake, stimulation of RNA synthesis, changes in polysomal profile, and the stimulated in vitro synthesis of alpha 2u-globulin. We now know that the alpha 2u consists of 4-5 related proteins only one of which is hepatically synthesized (isoelectric point, 5.2); the others are forms having different isoelectric points and are produced from the parent protein in the kidney. The nature of these renal alterations is unknown although deamidation and proteolytic modification of the parent protein are possible. The renal enzymes responsible for these changes will be studied. This model system is particularly valuable because alpha 2u is produced and excreted only by the adult male rat. The female may be made to synthesize and excrete this protein by repeated injections of testosterone. Therefore, this will serve as a unique system to study how the male sex hormones can function to influence the hepatic synthesis of proteins.